evaluate the efficacy and safety of evinacumab in pediatric patients with homozygous familial hypercholesterolemia

Conditions: Homozygous Familial Hypercholesterolemia

Summary: the primary objective for part a of the study is to assess the pharmacokinetics (pk) of evinacumab in pediatric patients with homozygous familial hypercholesterolemia (hofh). the primary objective for part b of the study is to demonstrate a reduction of low-density lipoprotein cholesterol (ldl-c) by evinacumab in pediatric (5 to 11 years of age) patients with hofh. the secondary objective for part a of the study is to evaluate the safety and tolerability of evinacumab administered intravenous (iv) in pediatric patients with hofh. the secondary objectives for part b of the study are: * to evaluate the effect of evinacumab on other lipid parameters (ie, apolipoprotein b (apo b), non-high-density lipoprotein cholesterol (non-hdl-c), total cholesterol (tc), lipoprotein a \[lp(a)\]) in pediatric patients with hofh * to evaluate the safety and tolerability of evinacumab administered iv in pediatric patients with hofh * to assess the pk of evinacumab in pediatric patients with hofh * to assess the immunogenicity of evinacumab in pediatric patients with hofh over time * to evaluate patient efficacy by mutation status

part a is phase 1b part b is phase 3

Eligibility criteria:
key inclusion criteria: 1. diagnosis of functional hofh by either genetic or clinical criteria as defined in the protocol 2. ldl-c \>130 mg/dl at the screening visit 3. body weight ≥15 kg 4. receiving stable maximally tolerated therapy\*at the screening visit \*maximally tolerated therapy could include a daily statin. 5. willing and able to comply with clinic visits and study-related procedures 6. parent(s) or legal guardian(s) must provide the signed informed consent form (icf). patients ≥5 years of age (or above age determined by the irb/ec and in accordance with the local regulations and requirements) must also provide informed assent forms (iafs) to enroll in the study, and sign and date a separate iaf or icf signed by the parent(s)/legal guardian(s) (as appropriate based on local regulations and requirements) key exclusion criteria: 1. background pharmacologic lmt, nutraceuticals or over-the-counter (otc) therapies known to affect lipids, at a dose/regimen that has not been stable for at least 4 weeks (8 weeks for pcsk9 inhibitors) before the screening visit and patient is unwilling to enter the run-in period 2. for patients entering part a, unable to temporarily discontinue apheresis from the baseline visit through the week 4 visit 3. receiving lipid apheresis, a setting (if applicable) and schedule that has not been stable for approximately 8 weeks before the screening visit or an apheresis schedule that is not anticipated to be stable over the duration of the treatment period (48 weeks). 4. plasmapheresis within 8 weeks of the screening visit, or plans to undergo plasmapheresis during part a or part b 5. presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins 6. newly diagnosed (within 3 months prior to randomization visit) diabetes mellitus or poorly controlled diabetes as defined in the protocol note: other protocol-defined criteria apply

Keywords: hofh